DESCRIPTION (provided by principal investigator): The purpose of this epidemiologic study is to determine the longitudinal associations of inflammatory factors, microvascular markers and atherosclerosis and the incidence of age-related hearing, olfactory and cognitive impairments. Mediating effects of statins and non-steroidal anti-inflammatory drugs (NSAIDs) on these associations will be examined and the 15-year incidence of hearing impairment and 10-year incidence of olfactory impairment will be determined. Subjects are participants in the population-based Epidemiology of Hearing Loss Study (EHLS) and were 48-92 years of age at the baseline examination (1993-95). The cohort was re-examined in 1998-2000 and 2003-05. Measures of carotid atherosclerosis were obtained in 1998-00. The proposed examination will use the same standardized protocols for hearing, olfaction, and cognitive testing used in the earlier phases and additional cognitive testing will be included. A standardized questionnaire about medical history, life-style factors and medication usage will be completed as an interview; carotid atherosclerosis will be re-measured by B-mode ultrasound scans; inflammatory markers (Il-6, TNF-a, and hsCRP) will be measured. Inflammatory markers also will be measured on stored serum samples from 1988-1990. Retinal microvascular measures from the Beaver Dam Eye Study will be available from multiple time points. Results from this study will have tremendous potential for leading to important translational research for new targeted treatments to reduce the effects of pro-inflammatory cytokines and atherosclerotic changes and to reduce the burden of these age-related health disorders. PUBLIC HEALTH RELEVANCE The proposed study will contribute important information about the roles of inflammation and vascular changes in hearing, olfaction and cognitive impairments. Linking these processes with common conditions of aging could lead to new treatments targeted at reducing the long-term effects of inflammation and atherosclerosis and improve health for tomorrow's elders.